A new antibody-drug compound shrank or halted the growth of
metastatic breast tumors in almost half of a group of patients whose
HER2-positive cancer had become resistant to standard therapies,
according to early data from a multicenter Phase II clinical trial led
by a Dana-Farber Cancer Institute researcher.

Ian Krop, MD, PhD,
principal investigator of the study, reports that the hybrid agent,
called T-DM1, shrank tumors by 30 percent or more in 40 percent of women
with confirmed HER2-positive cancers.

Another 13 percent had stable disease for at least six months, for a total clinical benefit rate of approximately 53 percent.

The median time before the disease progressed was 7.3 months,
including both responders and non-responders. Patients received T-DM1 as
long as it was effective and well-tolerated. A total of 110 women were
enrolled in the study.

T-DM1 is comprised of the cell-killing drug DM1 and is chemically
linked to trastuzumab, a monoclonal antibody. Trastuzumab selectively
binds to the HER2 growth signal receptor, which is highly overexpressed
in HER2-positive breast tumors. Approximately 20 percent of breast
cancers are HER2-postive.

Trastuzumab, developed by Genentech and sold under the name
Herceptin, has markedly improved the treatment of HER2-positive cancer,
but resistance to trastuzumab is a significant problem.

"The antibody binds to the HER2 protein on tumor cells and delivers
the drug (DM1) selectively to them — but not to normal cells," Krop
explained.

"This allows us to deliver high doses of the chemotherapy directly to
tumor cells. And at the same time, the antibody continues to block the
HER2 growth signals."

Krop said that one of the unique features of the study is that it is
the first to address a population of women with metastatic HER2-positive
breast cancer whose disease had progressed despite treatment with all
FDA-approved drugs for this disease (trastuzumab, lapatinib and several
chemotherapy agents).

On average, the women had metastatic breast cancer for three years
and previously received seven different drugs for their cancer.

Although patients experienced side effects that included nausea,
fatigue and lowered platelet counts, these effects were typically mild
and the drug in general was well-tolerated, said Krop.

In addition to the current study, T-DM1 is being tested in larger
Phase III trials comparing its effectiveness with that of other combined
therapies.